The Road to Quick COVID Vaccines Began 50 Years Ago

How did mRNA vaccines get rolled out so quickly during the pandemic? Part of it comes down to this Canadian researcher's half century of work.

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Part of the reason why researchers were able to successfully create COVID-19 mRNA vaccines so quickly was that the groundwork had begun decades before, and this included a major Canadian contribution.

For foundational work that enabled the delivery of mRNA vaccines to cells, providing the instructions for viral proteins that could be produced to launch an immune response, Pieter Cullis is now a 2022 Canada Gairdner International Award laureate.

“For the last 50 years — and I’m exaggerating there, 50 years — I’ve been trying to understand what lipids and membranes do,” says Cullis, professor of biochemistry and molecular biology at the University of British Columbia.

Cells make tens of thousands of lipids, and they are fundamental building blocks of the membranes that cover the cell and enclose various compartments. These membranes are like protective biological bubbles.

“What we did was we built what were termed model membranes, or little nanoparticles called liposomes, which were very simple versions of the biological membrane, and use those simple systems to understand what the roles of some of these different lipids were,” says Cullis.

“Now it turned out in the course of that, we found a way to those load cancer drugs into these lipid nanoparticles. This turned into an obvious way perhaps to deliver cancer drugs more specifically to tumours in the body.”

The cancer application alone was a major innovation for patients. Targeted delivery of cancer drugs reduced side effects, and in turn increased both safety and efficacy.

Fast forward to 2020, and the COVID-19 pandemic created an urgent need for a vaccine. mRNA vaccines could be quickly adapted to emerging infectious diseases, but none had ever been approved before. mRNA is also a large and fragile molecule that would have trouble making its way into cells so that its instructions can be read.

Cullis’s previous work on lipid nanoparticles helped researchers rapidly zero in on an ideal lipid shell to stabilize the vaccine for cell delivery.

“It just turned out that the lipid nanoparticle that we developed then got incorporated into the Pfizer/BioNTech COVID-19 vaccine,” says Cullis.

“And this, all the rest is history of course. That turned out to be incredible, 95 percent effective. And then three billion doses, you know, that have been delivered in the last year. So really an incredible story that goes way back, as I said, to 50 years ago when we first started trying to figure out what all these lipids and membranes actually do.”

This success story highlights the importance of basic research, which can enable applications far beyond what was originally envisioned.

“I’m often asked about the impact of getting the Gairdner Award. It’s obviously huge. It’s an amazing sense of honour with getting an award,” says Cullis.

“When you go back and you look at the number, of the people who have been awarded the Gairdner International in the past, and to be amongst that group is amazing. And the level of achievements, you feel somewhat inadequate in that crowd, let’s put it that way.”

He is quick to note that he couldn’t have made these achievements alone.

“Getting an award like this, you never do anything by yourself,” adds Cullis.

“And so really I’m just, I’m taking credit for the efforts of literally hundreds of people. Sometimes I think we should give awards to groups of people as opposed to individuals. I just have the luck of leading this particular group, it’s a large group.”

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